Cancer (tumor) is the number one disease as a cause of death in Japan. With exception of early stage gastric and cervical cancers by surgical operation, which yield fair numbers of success cases. Although a relatively good therapeutic results in lymphocytic leukemia by use of chemotherapy are known: other remaining many cancers, for instance, metastatic liver cancer, cancers of the lung, breast, pancreas, esophagus, gallbladder/cholangio, kidney, prostate, ovary, brain, as well as metastatic cancers such as pleural and abdominal carcinoma, achieved little progress in the past 30 years. (Non-patent Document 1: Fortune (2004), March issue).
Early detection at Stage 1 followed by curative surgery would yield improved therapeutic outcome as observed in gastric cancer, with exception of the liver cancer of which etiology is chronic infection of hepatitis viruses.
Under these circumstances, the present inventors have conducted research concerning the method of delivering macromolecular (or polymeric) drugs selectively to tumors, and discovered a new concept of EPR-effect (enhanced permeability and retention effect) and reported (Non-Patent Document 2: Cancer Research, 1986 (12) 46, 6787-6392). Further, the present inventors have developed and reported macromolecular cancer therapeutic agents such as SMANCS, the first macromolecular bound anticancer agent, and other macromolecular miceller anticancer drugs [Patent Document 1: WO 2004/103409; Patent Document 2: WO 2006/112361; Non-Patent Document 3: Adv. Drug Deliv. Rev. 6, 181-202 (1991); Non-Patent Document 4: J. Control. Release, 74, 47-61 (2001); and Non-Patent Document 5: Bioconj. Chem. 21, 797-802 (2010), etc.]